Chemistry
- An opiate antagonist, naloxone HCl is structurally related to
oxymorphone. It occurs as a white to slightly off-white powder with a pKa of
7.94. Naloxone is soluble in water and slightly soluble in alcohol. The pH
range of commercially available injectable solutions are from 3-4.5.
Naloxone HCl may also be known as N-allylnoroxymorphone HCl.

Storage/Stability/Compatibility
- Naloxone HCl for injection should be stored at room temperature
(15-30°C) and protected from light.

Sterile water for
injection is the recommended diluent for naloxone injection. When given as
an IV infusion, either D5W
or normal saline should be used. Naloxone HCl injec­tion should not be
mixed with solutions containing sulfites, bisulfites, long-chain or high
molecular weight anions or any solutions at alkaline pH.

Pharmacology
- Naloxone is considered to be a pure opiate antagonist and it has
basically no analgesic activity. The exact mechanism for its activity is
not understood, but it is be­lieved that the drug acts as a competitive
antagonist by binding to the mu, kappa, and sigma
opioid receptor sites. The drug apparently has its highest affinity for
the mu recep­tor.

Naloxone reverses the
majority of effects associated with high-dose opiate administration
(respiratory and CNS depression). In dogs, naloxone apparently does not
reverse the emetic actions of apomorphine.

Naloxone also has
other pharmacologic activity at high doses, including effects on
dopaminergic mechanisms (increases dopamine levels) and GABA antagonism.

Uses/Indications
- Naloxone
is used in veterinary medicine almost exclusively for its opiate reversal
effects, but the drug is being investigated for treating other conditions
(e.g., septic, hypovolemic or cardiogenic shock). Naloxone may also
be employed as a test drug to see if endogenous opiate blockade will
result in diminished tail-chasing or other self-mutilating behaviors.

Pharmacokinetics
- Naloxone is only minimally absorbed when given orally as it is rapidly
destroyed in the GI tract. Much higher doses are required if using this
route of ad­ministration for any pharmacologic effect. When given IV,
naloxone has a very rapid on­set of action (usually 1-2 minutes). If given
IM, the drug generally has an onset of action within 5 minutes of
administration. The duration of action usually persists from 45-90
minutes, but may act for up to 3 hours.

Naloxone is
distributed rapidly throughout the body with high levels found in the
brain, kidneys, spleen, skeletal muscle, lung and heart. The drug also
readily crosses the pla­centa.

Naloxone is
metabolized in the liver, principally via glucuronidative conjugation with
metabolites excreted into the urine. In humans, the serum half-life is
approximately 60-100 minutes.

Contraindications/Precautions/Reproductive Safety
- Naloxone is contraindicated in patients hypersensitive to it. It should
be used cautiously in animals that have preexisting cardiac abnormalities
or in animals that may be opioid dependent. The veterinary manu­facturer
states to use the drug “...cautiously in animals who have received
exceedingly large doses of narcotics. ... may produce an acute withdrawal
syndrome and smaller doses should be employed.” (Package Insert; P/M® Naloxone
HCl Injection—P/M; Mallinckrodt)

Naloxone is generally
considered to be non-teratogenic in animals, but has precipitated
withdrawal in opioid-dependent human fetuses.

Adverse
Effects/Warnings
- At usual doses, naloxone is relatively free of adverse effects in non-opioid
dependent patients. Because the duration of action of naloxone may be
shorter than that of the narcotic being reversed, animals that are being
treated for opioid intoxication or with symptoms of respi­ratory
depression should be closely monitored as additional doses of naloxone
and/or ven­tilatory support may be required.

Overdosage/Acute
Toxicity -
Naloxone is considered to be a very safe agent with a very wide margin of
safety, but very high doses have initiated seizures (secondary to GABA
an­tagonism?) in a few patients.

Drug Interactions
- Naloxone also reverses the effects of opioid agonists/antagonists such
as butorphanol, pentazocine or nalbuphine.

c) Smuts,G.L. 1975. An appraisal of naloxone
hydrochloride as a narcotic antagonist in the capture and release of wild
herbivores. J Am Vet Med Assoc 167:(7):559-561 Abstract: Naloxone hydrochloride was used as the narcotic
antagonist during capture operations conducted on 84 specimens of 11 game
species in the Kruger National Park, South Africa. It was found that 10 mg
of naloxone was sufficient to antagonize wide dosage ranges of etorphine
hydrochloride or fentanyl, used in combination with a variety of
tranquilizers. The absence of undesirable side effects and the fact that
naloxone can be administered without fear of over dosage make it a unique
and valuable drug in the capture and release of wild animals.

See
also:

Lance,W.R. 1991. New pharmaceutical tools for
the 1990's. Proceedings of the American Association of Zoo
Veterinarians 354-359

Monitoring
Parameters
-

1) Respiratory
rate/depth

2) CNS function

3) Pain associated
with opiate reversal

Client Information
- Should be used with direct professional supervision only.

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